In a multicenter phase 2 trial, in patients with ALK-positive NSCLC who progressed on crizotinib and were subsequently treated with ensartinib, longitudinal ctDNA analysis revealed ALK-dependent (G1269A, G1202R, and E1210K mutations) and ALK-independent (TP53 mutation) resistance mechanisms, thus underlining the significance of ctDNA analysis for monitoring tumor evolution [197]. This evidence concerns the gene ALK and neoplasm.